Sodium Carbonate → HCID 118075596, compound

HRID 1051700Notes

Reaction equation

HRID 1051700 reaction equation
[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[F:32])[C:12](B4OC(C)(C)C(C)(C)O4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:33])=[O:5])[CH2:3][CH2:2]1.Br[C:35]1[N:36]=[N:37][N:38]([CH3:40])[CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[F:32])[C:12]([C:35]4[N:36]=[N:37][N:38]([CH3:40])[CH:39]=4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:33])=[O:5])[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 217664104-Bromo-1-methyl-1H-1,2,3-triazoleHCID 123676582HCID 123676582, compound

Product 1

HCID 118075596HCID 118075596, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-cyclopropyl(5-(2-fluorophenoxy)-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.140 g, 0.31 mmol), 4-bromo-1-methyl-1H-1,2,3-triazole (0.050 g, 0.31 mmol), sodium carbonate (0.090 g, 0.85 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.010 g, 0.01 mmol) in 1,4-dioxane (10 mL) and water (3 mL) was stirred overnight at 80° C. The reaction mixture was cooled to room temperature, filtered through a short pad of Celite, and concentrated under vacuum. The residue was purified via preparative thin layer chromatography (eluting with 2:1, petroleum ether-ethyl acetate). The product was further purified by preparative-HPLC with the following conditions (Waters I): Column, XBridge C18, 19×150 mm, 5 um; Mobile Phase water (0.05% ammonium bicarbonate) and acetonitrile (35% to 65% acetonitrile in 10 min, flow rate: 20 mL/min); Detector: UV254&220 nm. This afforded (S)-cyclopropyl(5-(2-fluorophenoxy)-2-methyl-6-(1-methyl-1H-1,2,3-triazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)methanone (0.033 g, 26%) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 0.74-0.81 (m, 1H), 0.89-1.03 (m, 2H), 1.11-1.21 (m, 4H), 1.35-1.47 (m, 1H), 1.95-2.05 (m, 1H), 2.17-2.40 (m, 2H), 2.65-2.78 (m, 1H), 4.07 (s, 3H), 4.75-4.81 (m, 1H), 6.40-6.49 (m, 1H), 6.89-6.97 (m, 2H), 7.21-7.27 (m, 1H), 7.51 (d, J=8.40 Hz, 1H), 8.03 (s, 1H), 8.08 (d, J=8.40 Hz, 1H). MS (ESI, pos. ion) m/z 407 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through a short pad of Celite
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified via preparative thin layer chromatography (eluting with 2:1, petroleum ether-ethyl acetate)
  5. customThe product was further purified by preparative-HPLC with the following conditions (Waters I)
  6. customMobile Phase water (0.05% ammonium bicarbonate) and acetonitrile (35% to 65% acetonitrile in 10 min, flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-619bd6de2f8c46548098b77e128acad3
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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